Hyaluronic acid is a major constituent of connective tissues. It was discovered in bovine vitreous humor in 1934 by Karl Meyer [2] but its chemical structure was only able to be determined in the 1950ies [3, 4] (numerical references between square brackets relate to bibliographic references appearing at the end of the description).
It is mainly found in the epidermis (2-4 mg/mL), the dermis (˜0.5 mg/mL), the umbilical cord (˜4 mg/mL), the vitreous humor and in synovial liquid.
Hyaluronic acid is a polyelectrolyte, i.e. a polymer bearing ionizable groups capable of being dissociated in polar solvents, in order to form a charged polymer chain surrounded by more or less mobile counter-ions. The presence of charges gives to polyelectrolytic solutions remarkable physico-chemical properties corresponding to many applications.
Polyelectrolytes are used for their flow properties as thickeners or gelling agents, in cosmetics notably [1]. They are also used for their properties of adsorption to interfaces.
Further, they are widely present in biological media, which recommends their use within the scope of biomedical devices.
Because of its viscoelastic properties giving it great lubricating power, hyaluronic acid is used for viscosupplementation [5], the injection of hyaluronic acid in the joints having the goal of restoring homeostasia of synovial liquid by improving its flow properties and by promoting endogenous production of hyaluronic acid.
The properties of hyaluronic acid have also been exploited in ophthalmology [6]. It is used as a gel, as a protective agent of eye cells upon contact with surgical instruments and implants, during eye microsurgery operations. The main formulations of HA marketed for this type of applications are Healon® (Advanced Medical Optics, USA), Opegan® and OpeganHi® (Santen Pharmaceuticals, Japan).
With its great power for retaining water, hyaluronic acid plays a primordial role in moisturizing skin. It acts with collagen in order to give the cells some rigidity contributing to the flexibility of skin and, by being associated with proteoglycans of the skin, hyaluronic acid forms a network capable of preventing the passage of macromolecules (often toxic) and of facilitating that of small electrolytes in water.
For all these reasons, hyaluronic acid is used in the cosmetic field for formulating creams or gels.
A method for wet spinning of hyaluronic acid was developed in the years 1960-1970 for allowing the preparation of hyaluronic acid films having an oriented structure [7,8,9]. The method is the adaptation of a procedure and of a device developed for preparing DNA samples. In the wet spinning method described in document 9, a solution of potassium hyaluronate (2.5 to 3 mg/mL in a 0.1M KCl solution) is continuously extruded through a die including 720 cylindrical channels each having a diameter of 70 μm and a length of 1.5 mm. The potassium hyaluronate solution is extruded in a bath containing 75-80% ethyl alcohol in 0.1M KCl. The potassium hyaluronate fibers precipitate and are then grouped in a bundle and wound on a rotary cylinder. Said fibers are then dried which leads to the formation of a film by coalescence.
Short fibers (nanofibers) of hyaluronic acid, grouped as membranes, have also been obtained by the electro-spinning and blowing-assisted electro-spinning technique [10,11].
With the mentioned methods, it is not possible to obtain hyaluronic acid filaments but only membranes consisting of networks of nanofibers, i.e. fibers of very short length.
Moreover, materials based on hyaluronic fibers were able to be obtained by cross-linking of hyaluronic acid in the presence of cross-linking agents of the carbodiimide or epoxide type (cross-linking agents, a non-exhaustive list of which is for example mentioned in document US 2007066816). These materials however have the non-negligible disadvantage of being toxic for humans, which severely limits their interest in all uses in vivo. Further, these materials are insoluble in water.